F. Pisani et al., Neuroprotective effects of lamotrigine and remacemide on excitotoxicity induced by glutamate agonists in isolated chick retina, EXP NEUROL, 170(1), 2001, pp. 162-170
The possible neuroprotective effects of two recently developed antiepilepti
c compounds, lamotrigine (LTG) and remacemide (REMA), against glutamate ago
nist-induced excitotoxicity have been investigated in the isolated chick em
bryo retina model. Retina segments from 15- or Is-day-old embryos were incu
bated in 1 ml of balanced salt solution, at 25 degreesC for 30 min, in the
presence or absence of N-methyl-D-aspartate (NMDA), kainic acid (KA), or al
pha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (10 to 200 m
uM). LTG, REMA, and the active desglycinyl metabolite of REMA (d-REMA) (10-
200 muM) were added separately 5 min before glutamate agonists. Retina dama
ge was assessed after 24 h (i) by measuring LDH activity present in the med
ium, expressed as percentage of total retina LDH activity, and (ii) by hist
ological analysis of retina specimens through scoring for the presence or a
bsence of edema, necrosis, nuclear pyknosis, and cell layer damage. LTG, RE
MA, and d-REMA reduced LDH release produced by NMDA 58-70% in a dose-depend
ent manner, with d-REMA being the most potent (EC50: d-REMA, 25.75 +/-3.27
muM; REMA 64.75 +/-7.75 muM; LTG, 60.50 +/-6.80 muM; P < 0.001). The drugs
had less effect on the LDH release produced by AMPA and Kk Histological ana
lysis confirmed these biochemical results, with all three compounds reducin
g edema and the number of necrotic and pyknotic nuclei in the ganglion laye
r. d-REMA provided almost complete protection of the ganglion cell layer ag
ainst damage produced by NMDA. Combinations of d-REMA and LTG showed additi
ve rather than potentiative effects against NMDA-induced cell injury. The p
resent data provide pharmacological evidence that LTG, REMA, and d-REMA dec
rease glutamate agonist-induced excitotoxicity in isolated chick retina, fi
ndings that might have therapeutic implications for various neurological (C
) 2001 Academic Press.